The prevalence of anal pre-cancer and cancer have substantially increased during the past decades. This is especially true for HIV-positive men and women, and for men who have sex with men (MSM);an increase has been also seen, however, in men and women in the general population who do not belong to these high-risk groups. In HIV-positive individuals, anal cancer has now become a major malignancy, representing an urgent medical need. The natural history of anal cancer closely resembles that of cervical cancer. Both cancers occur almost exclusively as the consequence of persistent infection with high-risk human papillomaviruses (hr-HPV), and both cancers develop through pre-cancerous states characterized by neoplastic transformation of the respective epithelial tissues (causing anal- / cervical intraepithelial neoplasia;AIN and CIN). Reduction of cervical cancer-related mortality in the developed world has resulted from implementation of screening technologies allowing detection and timely treatment of CIN before it progresses to cervical cancer. It is therefore likely that the key to reduction of anal cancer-related mortality and morbidity lies in early detection and treatment of AIN. Current methods of AIN screening involve anal cytology and high resolution anoscopy (HRA), followed by HRA-guided biopsy. Anal cytology requires substantial infrastructure and has limited sensitivity, specificity and positive predictive value. Hence, the development of new technologies for detection of AIN is a high priority. Ideally, new tests for AIN should be easy to perform and provide superior clinical performance. Ideally they would also provide prognostic value indicating increased risk of progression. Previously, Arbor Vita Corporation (AVC) has developed a rapid, lateral flow-based test for detection of CIN and cervical cancer. The test is based on detection of the hr-HPV-E6 oncoprotein. E6 is necessary for initiation and maintenance of cervical epithelia cell transformation, and therefore, it promises high clinical sensitivity and specificity when used as a diagnostic and prognostic marker. Under this SBIR Phase I grant proposal, AVC, in collaboration with Dr. Palefsky's group at the University of California, San Francisco (UCSF), proposes to develop a prototype lateral flow-based test for detection of oncogenic HPV infection and AIN, the "Rapid Test for Anal Neoplasia", using the existing CIN and cervical cancer lateral flow test as a platform. Due to the lateral flow format, the test promises to be cost-effective, easy to perform in a point-of-care setting, and potentially amenable to self-sampling and - testing. We further propose to determine the clinical sensitivity for AIN and prognostic value to predict progression from AIN1 to AIN 2 or 3 of the Rapid Test for Anal Neoplasia. This test will greatly facilitate identification of those most in need of further diagnostic workup and treatment to prevent anal cancer. PUBLIC HEALTH RELEVANCE: Human papillomavirus induced anal cancer shows increasing prevalence in men having sex with men, in HIV positive individuals, and, to a lower extent, in HIV negative men and women. Early detection of anal pre-cancerous intraepithelial lesions (AIN) is the key to efficient treatment, which could reduce anal cancer related mortality. The applicants propose the development of a simple lateral flow based Rapid Test for Anal Neoplasia, which detects HPV infection related AIN and anal cancer, using the HPV-E6 oncoprotein.